Expression and role of p16 and GLUT1 in malignant diseases and lung cancer: A review

Abstract

Non-small cell lung cancer (NSCLC) is the leading cause of cancer death and in most cases it is often diagnosed at an advanced stage. Many genetic and microenvironmental factors are able to modify the cell cycle inducing carcinogenesis and tumor growth. Among the metabolic and genetic factors that come into play in carcinogenesis and tumor cell differentiation and growth there are two different proteins that should be considered which are glucose transporters (GLUTs) and p16^INK4 The first are glucose transporters which are strongly involved in tumor metabolism, notably accelerating cancer cell metabolism both in aerobic and anaerobic conditions. There are different subtypes of GLUT family factors of which GLUT 1 is the most important and widely expressed. By contrast, p16 is mainly a tumor-suppressor protein that acts on cyclin-dependent kinase favoring cell cycle arrest in the G1 phase. Our search focused on the action of the aforementioned factors.

Keywords: Glucose transporters; lung cancer; p16 expression.

Figure 1

p16 is able to inhibit the action of cyclin D kinase which is responsible for retinoblastoma protein (pRb) phosphorylation leading to pRb inactivation and cell cycle progression stimulating the S phase. By contrast, p16 action leads to G1 arrest of the cell cycle.

Figure 2

Effects of GLUT‐1 in relation to hypoxia. Hypoxia condition is a tissue oxygen tension of about 1% which stimulates tumor cells to produce HIF‐1α which in turn induces both the production of GLUT‐1 and VEGF; the first increase glucose uptake and cell metabolism whilst the second favors neoangiogenesis.